Several new neural prostheses are being investigated that will require intracortical stimulation of cerebral cortex with multiple microelectrodes. Studies of intracortical stimulation with single penetrating microelectrodes have established safe levels of stimulation under certain stimulating conditions, but more information is needed about the safe limits for multiple, closely spaced, penetrating microelectrodes such as would be used in advanced visual prostheses. This is one of the objectives of this research project. Progress has been made on understanding the causes of tissue damage that can occur at high levels of stimulation. In order to minimize tissue damage, more information will be obtained on methods of preventing damage, the safety of new biomaterials, as well as better methods of physically stabilizing microelectrodes in neural tissue. The possibility of using multicontact, silicon microelectrodes with long shanks to access buried cortical tissue will also be investigated. Silicon microelectrodes are presently being fabricated by another contractor. Histopathological, neurochemical and neurophysiological techniques must be applied to determine the effects of both acute and chronic activation of cortical tissue. When physiological or histopathological evidence of detrimental alteration of neural function or structure is noted, research will be undertaken to determine the mechanism(s). Electrodes being used include discrete wire intracortical microelectrodes as well as silicon microcircuit microelectrodes furnished by the Project Officer. The results of this work will be of value not only to neural prosthesis investigators, but also to neurophysiologists who utilize electrical stimulation as a tool in fundamental studies of the nervous system.